(Applicant's Abstract) This renewal SCOR program continues basic and clinical studies to address molecular mechanisms of lung development as well as the pathogenesis and prevention of bronchopulmonary dysplasia (BPD). This disease continues to be a major cause of morbidity and mortality in premature infants even in the era of antenatal corticosteroid treatment and surfactant replacement. The overall hypothesis of the SCOR program is that BPD is the result of injury and abnormal repair in an immature lung, and that basic studies related to processes of normal lung development, the inflammatory response, and effects of inhaled nitric oxide will provide important information regarding the pathogenesis and prevention of BPD. The SCOR involves 18 investigators from the Schools of Medicine and Dental Medicine at the University of Pennsylvania plus three investigators from the School of Medicine at the University of Utah, and consists of five basic science projects, each with a clinical component, and three Cores. The goals of the basic science projects are to investigate differentiation of alveolar type II cells and the roles of the hydrophobic surfactant proteins (Project 0001), signaling mechanisms in endothelial cell differentiation and vascular development (Project 0005), molecular events in the cellular inflammatory response after lung injury (Project 0006), and the role and regulation of key growth factors in lung development and the fibroproliferative response (Project 0004). These projects use lung tissue and cells, rats and transgenic mice as experimental models. The Tissue Culture Core provides cultured lung tissue and cells and maintains a repository of fetal and postnatal human lung tissue. An off-site basic science project utilizes a unique premature lamb model of BPD to investigate effects and mechanisms of inhaled nitric oxide on development of lung disease (Project 0007). The clinical focus of the program is the pathogenesis of BPD and prevention by inhaled nitric oxide. The Clinical Core enrolls premature infants in SCOR protocols and collects extensive clinical data and samples for studies by the basic science projects. This patient population includes infants participating in a NIH-funded multicenter clinical trial of inhaled nitric oxide to prevent BPD. The Director of the SCOR is an experienced investigator in lung development and the participating investigators include both senior researchers and well trained, promising younger investigators, each with specific expertise in their respective areas of study. The program is highly interactive with close collaborations between projects and with the clinical component. The renewal SCOR represents a multidisciplinary, highly integrated, and thematic translational research program related to the pathogenesis and prevention of BPD.